The University of Pittsburgh and University of Pittsburgh Cancer Institute propose to conduct a Specialized Program of Research Excellence (SPORE) in Skin Cancer. The overall goals of the University Pittsburgh Skin Cancer SPORE are to improve the detection and treatment of skin cancer. The SPORE program will consist of six translational research projects in skin cancer, four cores including an administrative core, a developmental research program and a career development program. The University of Pittsburgh Skin Cancer SPORE will use an interdisciplinary approach to meet its objectives by carrying out projects with co- investigators in basic, applied and clinical science. It is also organ-specific in that its approach and all projects will test hypotheses about skin cancer biology, susceptibility, detection, or treatment. The long-term translational research projects that will serve as the basis for improving the outcome of patients diagnosed with skin cancer. The six main projects include: (1) Chemoprevention of Melanoma with Sulforaphane; (2) Multiple Antigen-Engineered DC Immunization and IFN? Boost for Metastatic Melanoma; (3) Polarized Dendritic Cells Guide Melanoma-Specific Responses; (4) Therapeutic Immune Targeting of EphA2 Expressed by Melanoma and Its Tumor-Associated Vasculature; (5) Delineating the DNA Repair pathways impacting alkylating agent efficacy in the treatment of Melanoma; (6) Augmentation of Dendritic Cell-based Immunotherapy for Sezary Syndrome by T-regs depletion. The four research cores will interact closely to assist the main research projects, developmental research projects and the career development investigators in carrying out translational skin cancer research. The research cores are: Core A. Administrative Core; Core B. Tissue Core; Core C. Immunological Monitoring and Cellular Products Laboratory (IMCPL); Core D. Biostatics. The Administrative Core will solicit feedback from the Internal and External Scientific Advisory Boards and provide scientific, regulatory and fiscal oversight for the SPORE program. The Skin SPORE investigators will work together to synergistically achieve the goals of the program and will also interact with investigators from SPOREs at other institutions to improve the outcome of patients with skin cancer.